肿瘤细胞治疗研究
英文原题：Allogeneic γδT Cells in Glioblastoma
⚠ 该试验的登记信息已有 13 个月未更新， 页面上显示的「招募中」可能已经失效。联系研究中心之前，建议先到 ClinicalTrials.gov 核对登记原文的最新状态与联系方式。
这是一项分期未标注的注册临床试验，评估异体 T 细胞治疗胶质母细胞瘤的安全性、可行性及初步疗效。当前状态：招募中。计划入组 18 例。试验地点：中国 · 北京、郑州（共 3 个中心，其中中国 3 个）。登记号：NCT07144735。
不限性别 · ≥ 18 Years 且 ≤ 70 Years
纳入标准： 1. 男女均可，年龄18–70岁（含两端）； 2. 至少有一个可评估病灶，既往活检或病理组织学证实为WHO IV级胶质母细胞瘤，且综合治疗后影像学提示持续进展或复发； 3. Karnofsky体能状态（KPS）≥60%； 4. 预期生存期>4周； 5. 入组前至少4周已完成放疗或全身治疗（包括替莫唑胺/贝伐珠单抗或其他药物）。按CTCAE 6.0标准，既往治疗相关毒性须恢复至≤1级，脱发或白斑等毒性除外； 6. 能够接受增强MRI检查； 7. 骨髓和器官功能充分，具体如下：白细胞≥3×10⁹/L；中性粒细胞绝对计数>1×10⁹/L；血红蛋白≥90 g/L；血小板≥80×10⁹/L；ALT和AST<机构正常值上限（ULN）的1.5倍；血清肌酐<机构ULN的1.5倍；总胆红素<机构ULN的1.5倍；PT和PTT≤机构ULN的1.25倍； 8. 无明显遗传性疾病； 9. 心功能正常，左心室射血分数>55%； 10. 无出血性疾病及凝血障碍； 11. ABOUT γδT细胞输注前48小时内血培养未检出细菌、真菌或病毒，且无脑膜炎迹象； 12. 有生育能力的女性须在治疗开始前7天内妊娠检测阴性；受试者愿意在临床试验期间及末次细胞输注后6个月内采取避孕措施（激素或屏障避孕，或禁欲）。若试验期间怀孕或怀疑怀孕，须立即告知治疗医生； 13. 已签署书面知情同意书。 排除标准： 1. 活动性乙型/丙型肝炎、HIV感染或其他未治疗的活动性感染； 2. 妊娠期或哺乳期女性； 3. 器官衰竭； 4. 需要免疫或激素治疗的慢性疾病； 5. 对免疫治疗及相关细胞过敏； 6. 未控制的并发疾病； 7. 精神疾病或社会环境因素可能妨碍遵守研究要求； 8. 有器官移植史或正在等待器官移植。
Inclusion Criteria: 1. Male or female, age 18-70 years old (both ends included) 2. At least one evaluable lesion with previous biopsy or pathohistologic confirmation of glioblastoma (WHO grade IV), with imaging suggestive of continued progression or recurrence after comprehensive treatment 3. Karnofsky Performance Status (KPS) ≥ 60% 4. Life expectancy \> 4 weeks 5. Patients who completed radiotherapy or systemic therapies (including temozolomide/bevacizumab or other agents) for at least 4 weeks prior to enrollment. All prior treatment-related toxicities should be defined as ≤ grade 1 (except for toxicities such as alopecia or leukoplakia) according to the Common Terminology Standard for Adverse Events (CTCAE 6.0) 6. Must be able to undergo an MRI with contrast 7. Must have adequate organ and marrow function as defined below: * White blood cell count (WBC) ≥ 3 x 10\^9/L * Absolute neutrophil count (ANC) \> 1 x 10\^9/L * Hemoglobin (Hb) ≥ 90 g/L * Platelet (PLT) ≥ 80×10\^9/L * Albumin transaminase (ALT) \& albumin transaminase (AST) \< 1.5 × institutional upper limit of normal (ULN) * Serum creatinine (Cr) \< 1.5 x institutional ULN * Total bilirubin \< 1.5 x institutional ULN * PT \& PTT ≤ 1.25 x institutional ULN 8. No obvious hereditary diseases 9. Normal cardiac function with left ventricular ejection fraction \>55% 10. No bleeding and coagulation disorders 11. Absence of positive blood cultures for bacteria, fungus, or virus within 48-hours prior to ABOUT γδT cell infusion and/or there aren't any indications of meningitis 12. Fertile women must have had a pregnancy test with a negative result within 7 days prior to the start of treatment, and subjects are willing to use contraception (hormonal or barrier method of birth control or abstinence) during the clinical trial and for 6 months after the last cell infusion; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately 13. Signed, written informed consent Exclusion Criteria: 1. Active hepatitis B or C virus, HIV infection, or other untreated active infection 2. Pregnant and lactating women 3. Participants with organ failure 4. Participants with a chronic disease requiring immunologic or hormonal therapy 5. Participants with an allergy to immunotherapy and related cells 6. Participants with uncontrolled intercurrent illness 7. Participants with psychiatric illness/social situations that would limit compliance with study requirements 8. Participants with a history of organ transplantation or who are awaiting organ transplantation
以上为辅助阅读译文。是否适合入组须由主治医生判断，最终以登记平台与研究者确认为准。
主要终点：Incidence of Adverse Events (AEs) · Defined as the incidence of ≥ Grade 3-4 adverse events related to ABOUT γδT cells according to common terminology criteria for adverse events (CTCAE) v6.0. · 3 months following ABOUT γδT cells administration；Incidence of Dose-Limiting Toxicities (DLTs) · Defined as events attributable to ABOUT γδT cells infusion within 28 days post-infusion. Grade 3-4 acute graft-versus-host disease (GvHD) according to the Mount Sinai Acute GvHD International Consortium criteria; Grade 3 or higher cytokine release syndrome (CRS) lasting more than 2 weeks, according to American Society for Transplantation and Cellular Therapy (ASTCT) criteria; Any ABOUT γδT cells-related AE requiring intubation; Grade 4 non-hematologic toxicities. · 28 days following initial treatment with ABOUT γδT cells
次要终点：Objective Response Rate (ORR)；Duration of response (DOR)
剂量1：7×10⁷个ABOUT γδT细胞，每3–4周局部给药一次。
剂量2：1.1×10⁸个ABOUT γδT细胞，每3–4周局部给药一次。
剂量3：1.6×10⁸个ABOUT γδT细胞，每3–4周局部给药一次。
这项首次人体临床研究旨在评估局部给予异基因γδ T细胞治疗多形性胶质母细胞瘤（GBM）患者的安全性和可行性。该细胞经基因编辑敲除ARIH1和BCL11b，命名为ABOUT γδT细胞；通过局部给药选择性靶向并清除残留GBM细胞。ABOUT意为ARIH1和BCL11b敲除γδ T细胞。
This first-in-human clinical study aims to evaluate the safety and feasibility of locally delivered, allogeneic γδ T cells (genetically edited with ARIH1 and BCL11b knockout, designated ABOUT γδT cells) in patients with glioblastoma multiforme (GBM). The engineered effector cells are delivered via localized administration to selectively target and eliminate residual GBM cells. ABOUT: ARIH1 and BCL11b knockOUT γδ T cells.
MEMBER ACCOUNT
登录成功会直接打开下一页。
